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Final Progress Reports: Cornell University: Developmental Immunotoxicologic Appraisal of DMSA

Superfund Research Program

Developmental Immunotoxicologic Appraisal of DMSA

Project Leader: Rodney R. Dietert
Grant Number: P42ES005950
Funding Period: 1995 - 2000
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

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Final Progress Reports

Year:   1999 

Previous results suggested that dietary protein level probably influenced maternal Pb bioavailability--suggesting the need for more protein level work. The results of the pulsed embryonic exposure data from year 3 in chickens were used to design developmental window trials in the rat. While some assays are still underway, it is clear that exposure of the pregnant rat to equal amounts of Pb (as lead acetate) during early (days 3-9 of pregnancy) versus late (days 15-21 of pregnancy) gestation produces different immunotoxic outcomes. Pb-induced depression of the hallmark Th1-associated function (the delayed type hypersensitivity (DTH) response) was evident only following the late gestational exposure of the female offspring. These results parallel the year 3 chicken data suggesting that the DTH response is unaffected by pulsed early embryonic exposure to Pb. Along with a functional change, an increase in the relative number of blood monocytes as well as an increase in thymic weight was observed in females after exposure to Pb late in gestation. In contrast, males did not markedly differ in the DTH response after late gestational exposure to Pb although a significant increase in interleukin-12 concentration was produced. Early embryonic exposure to Pb can influence certain macrophage functions persistently. In male offspring exposed to Pb early in gestation, a decrease in macrophage nitrite production was observed. Female offspring nitrite production was also decreased with Pb treatment, although the decrease was not significant. These results indicate that critical windows of developmental exposure to Pb exist and that gender may influence the immunotoxic outcome.

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